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The Effects of Proinflammatory Cytokines and TGF-beta, on The Fibroblast Proliferation (Proinflammatory Cytokines과 TGF-beta가 섬유모세포의 증식에 미치는 영향)

  • Kim, Chul;Park, Choon-Sik;Kim, Mi-Ho;Chang, Hun-Soo;Chung, Il-Yup;Ki, Shin-Young;Uh, Soo-Taek;Moon, Seung-Hyuk;Kim, Yong-Hoon;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.861-869
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    • 1998
  • Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

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The Significance of Plasma Urokinase-type Plasminogen Activator and Type 1 Plasminogen Activator Inhibitor in Lung Cancer (폐암에서 혈장 Urokinase-Type Plasminogen Activator 및 Type 1 Plasminogen Activator Inhibitor의 의의)

  • Park, Kwang-Joo;Kim, Hyung-Jung;Ahn, Chul-Min;Lee, Doo-Yun;Chang, Joon;Kim, Sung-Kyu;Lee, Won-Young
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.516-524
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    • 1997
  • Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{\pm}0.3ng/mL$ in controls, $1.0{\pm}0.3ng/mL$ in benign lung disease patients and $0.9{\pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{\pm}6.7ng/mL$ in controls, $14.9{\pm}6.3ng/mL$ in benign lung disease patients, and $22.1{\pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{\pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{\pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{\pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{\pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{\pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{\pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{\pm}0.6ng/mL$ in stage II, $0.7{\pm}0.4ng/mL$ in stage IIIA, $0.7{\pm}0.4ng/mL$ in stage IIIB, and $0.7{\pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{\pm}8.7ng/mL$ in stage II, $18.4{\pm}4.9ng/mL$ in stage IIIA, $25.3{\pm}9.0ng/mL$ in stage IIIB, and $21.5{\pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{\pm}0.4ng/mL$ in T1-3 and $0.7{\pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{\pm}5.6ng/mL$ in T1-3 and $26.1{\pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{\pm}0.4ng/mL$ in M0 and $0.7{\pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{\pm}8.3ng/mL$ in M0 and $21.5{\pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.

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Incorporating Social Relationship discovered from User's Behavior into Collaborative Filtering (사용자 행동 기반의 사회적 관계를 결합한 사용자 협업적 여과 방법)

  • Thay, Setha;Ha, Inay;Jo, Geun-Sik
    • Journal of Intelligence and Information Systems
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    • v.19 no.2
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    • pp.1-20
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    • 2013
  • Nowadays, social network is a huge communication platform for providing people to connect with one another and to bring users together to share common interests, experiences, and their daily activities. Users spend hours per day in maintaining personal information and interacting with other people via posting, commenting, messaging, games, social events, and applications. Due to the growth of user's distributed information in social network, there is a great potential to utilize the social data to enhance the quality of recommender system. There are some researches focusing on social network analysis that investigate how social network can be used in recommendation domain. Among these researches, we are interested in taking advantages of the interaction between a user and others in social network that can be determined and known as social relationship. Furthermore, mostly user's decisions before purchasing some products depend on suggestion of people who have either the same preferences or closer relationship. For this reason, we believe that user's relationship in social network can provide an effective way to increase the quality in prediction user's interests of recommender system. Therefore, social relationship between users encountered from social network is a common factor to improve the way of predicting user's preferences in the conventional approach. Recommender system is dramatically increasing in popularity and currently being used by many e-commerce sites such as Amazon.com, Last.fm, eBay.com, etc. Collaborative filtering (CF) method is one of the essential and powerful techniques in recommender system for suggesting the appropriate items to user by learning user's preferences. CF method focuses on user data and generates automatic prediction about user's interests by gathering information from users who share similar background and preferences. Specifically, the intension of CF method is to find users who have similar preferences and to suggest target user items that were mostly preferred by those nearest neighbor users. There are two basic units that need to be considered by CF method, the user and the item. Each user needs to provide his rating value on items i.e. movies, products, books, etc to indicate their interests on those items. In addition, CF uses the user-rating matrix to find a group of users who have similar rating with target user. Then, it predicts unknown rating value for items that target user has not rated. Currently, CF has been successfully implemented in both information filtering and e-commerce applications. However, it remains some important challenges such as cold start, data sparsity, and scalability reflected on quality and accuracy of prediction. In order to overcome these challenges, many researchers have proposed various kinds of CF method such as hybrid CF, trust-based CF, social network-based CF, etc. In the purpose of improving the recommendation performance and prediction accuracy of standard CF, in this paper we propose a method which integrates traditional CF technique with social relationship between users discovered from user's behavior in social network i.e. Facebook. We identify user's relationship from behavior of user such as posts and comments interacted with friends in Facebook. We believe that social relationship implicitly inferred from user's behavior can be likely applied to compensate the limitation of conventional approach. Therefore, we extract posts and comments of each user by using Facebook Graph API and calculate feature score among each term to obtain feature vector for computing similarity of user. Then, we combine the result with similarity value computed using traditional CF technique. Finally, our system provides a list of recommended items according to neighbor users who have the biggest total similarity value to the target user. In order to verify and evaluate our proposed method we have performed an experiment on data collected from our Movies Rating System. Prediction accuracy evaluation is conducted to demonstrate how much our algorithm gives the correctness of recommendation to user in terms of MAE. Then, the evaluation of performance is made to show the effectiveness of our method in terms of precision, recall, and F1-measure. Evaluation on coverage is also included in our experiment to see the ability of generating recommendation. The experimental results show that our proposed method outperform and more accurate in suggesting items to users with better performance. The effectiveness of user's behavior in social network particularly shows the significant improvement by up to 6% on recommendation accuracy. Moreover, experiment of recommendation performance shows that incorporating social relationship observed from user's behavior into CF is beneficial and useful to generate recommendation with 7% improvement of performance compared with benchmark methods. Finally, we confirm that interaction between users in social network is able to enhance the accuracy and give better recommendation in conventional approach.